1. Field of Invention
The present disclosure relates to a compound for inhibiting glutathione s-transferase omega 1 activity, a pharmaceutical composition containing thereof, and a method for synthesizing the same.
2. Description of Related Art
Nowadays, Multi-Drug Resistance (MDR) is believed to be one of the essential topics of pharmaceutical drug research and development on cancer therapy. In addition to the well known channel proteins like p-glycoprotein, MRP1, ABCG2, etc, protein enzymes as metabolic drugs have also been gradually given attention in the field of pharmaceutical drug development. In which, Glutathione S-Transferase (GST) family protein have been playing a critical role.
The GSTs is a phase II metabolic enzyme that favors detoxification of foreign substances of cells; the foreign substances will be linked with glutathione by the GSTs in order to reduce their toxicities. Thus, GST family proteins have been found to be highly expressed in various cancer cells. However, both the fundamental and clinical researches indicated that the GSTs have been an important factor involved in drug resistance.
It was found in many studies that one of a protein of the GSTs, GST pi, was essential in association with the acquired resistance to certain anticancer drugs, and thus the GST pi inhibitors have been put under the spotlight by pharmaceutical drug researchers and developers as a main discovering target so as to eliminate such a drug resistance effect. For instance, Telik Biopharmaceutical Company received a great amount of patents of various GST pi inhibitors, some of which have been made as drugs, such as TELCYTA® (Canfosfamide HCl) and TELINTRA® (Ezatiostat HCl, TLK199).
Other isoforms of GSTs, namely GST omega family, such as GST omega 1-1 have been found to be closely associated with drug resistance effects against adriamycin, etoposide, and platinum anticancer drugs. Furthermore, a depletion of GST omega 1-1 in cancer cells circumvents drug resistances against arsenic trioxide, cisplatin, daunorubicin, and etoposide.
Nevertheless, inhibitors of GST omega 1 are yet to be discovered nor developed for addressing the drug resistance effects in cancer cells.